Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug used and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) whole-plant cannabis extracts. Male Sprague-Dawley rats were trained to nose-poke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily 1 h sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared with CANCBD or VEH, and the number of...

Cannabinoids, the bioactive constituents of cannabis, exert a wide array of effects on the brain by engaging Type 1 cannabinoid receptor (CB1R). Accruing evidence supports that cannabinoid action relies on context-dependent factors, such as the biological characteristics of the target cell, suggesting that cell population-intrinsic molecular cues modulate CB1R-dependent signaling. Here, by using a yeast two-hybrid-based high-throughput screening, we identified BiP as a potential CB1R-interacting protein. We next found that CB1R and BiP interact specifically in vitro , and mapped the interaction site within the CB1R C -terminal (intracellular) domain and the BiP C -terminal (substrate-binding) domain-α. BiP selectively shaped agonist-evoked CB1R signaling by blocking an “alternative” Gq/11 protein-dependent signaling module while leaving the “classical” Gi/o protein-dependent inhibition of the cAMP pathway unaffected. In situ proximity ligation assays conducted on brain samples from various genetic mouse mo...

Previous research has implicated the positive modulation of anandamide, an endocannabinoid neurotransmitter, on feeding behavior. Anandamide is particularly noteworthy as it shares a similar mechanism of action with tetrahydrocannabinol, the primary psy...

Cannabis is one of the oldest and the world’s third most popular recreational drug, after alcohol and tobacco. Several studies indicate that cannabis use during pregnancy is increasing due to the fact that it is easily accessible and is considered to be...

Dravet syndrome (DS) is an epileptic encephalopathy that still lacks biomarkers for epileptogenesis and its treatment. Dysfunction of NaV1.1 sodium channels, which are chiefly expressed in inhibitory interneurons, explains the epileptic phenotype. Understanding the network effects of these cellular deficits may help predict epileptogenesis. Here, we studied θ-γ coupling as a potential marker for altered inhibitory functioning and epileptogenesis in a DS mouse model. We found that cortical θ-γ coupling was reduced in both male and female juvenile DS mice and persisted only if spontaneous seizures occurred. θ-γ Coupling was partly restored by cannabidiol (CBD). Locally disrupting NaV1.1 expression in the hippocampus or cortex yielded early attenuation of θ-γ coupling, which in the hippocampus associated with fast ripples, and which was replicated in a computational model when voltage-gated sodium currents were impaired in basket cells (BCs). Our results indicate attenuated θ-γ coupling as a promising early i...

Chronic pain effects over 100 million Americans. Some individuals suffering from chronic pain may utilize cannabis for analgesia. Increasing marijuana legality in the United States calls for an investigation of the neurophysiological effects of cannabis...

Endo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release. However, the molecular mechanisms u...

Supraoptic neurones are regulated by estrogen (E2) and express ER-β. Physiological concentrations of E2 inhibit NMDA-stimulated vasopressin (VP) release from explants of the hypothalamo-neurohypophyseal systems. To test the hypothesis that this effect of E2 is mediated by ER-β, tetrahydrochrysene, R,R-enantiomer (R,R-THC), a compound which is an ER-β antagonist and an ER-α agonist was used (1). Explants from male Sprague-Dawley rats (129-150g, n=5-7/group) were perifused and hormone release was measured in timed fractions by radioimmunoassay. Following a 4hr equilibration period, explants were either exposed to 50μM NMDA for 3hrs. or maintained in basal medium. E2 (50pg/ml) and/or R,R-THC (55.2nM, a 300fold excess relative to E2) were present in the medium of some explants throughout the entire perifusion. At this concentration, R,R-THC did not alter basal VP release. In basal medium, NMDA caused an increase in VP release that was significantly elevated compared to control explants for approximately 1hr (p...

Research shows that various recreationally used substances have distinctive effects on neuromodulation, and those effects can produce observable health outcomes. For example, while alcohol is associated with increased inflammation in the body, marijuana...

Amyotrophic lateral sclerosis (ALS) is a progressive and disabling disease characterized by muscle denervation, weakness and atrophy. It is caused by the progressive loss of upper and lower motor neurons triggered by different factors. The disease has n...